Cancer stem cells in resistance to Photodynamic Therapy

VILCHES, ML ; MILLA, L; PRUCCA, CG; CAPUTTO, BL; RIVAROLA, VA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. LIII Reunion Anual de la Sociedad Argentina de Investigaciones en Bioquimica y Biologia Molecular.; 2017

Photodynamic therapy (PDT) is an oncologic treatment. It is basedon the administration of a photosensitizer and its activation throughvisible light. The main problem of all oncological treatments, includingPDT, is the occurrence of resistant cells. It is proposed that asmall fraction of neoplastic cells, called cancer stem cells (CSCs),are the responsive of tumor regeneration and the resistance to thetherapies. In our laboratory, we have obtained human cells of skincancer (SCC-13) and glioblastoma (T98G), resistant to several cyclesof PDT with Me-ALA. The resistant populations present characteristicsof CSCs, such as a higher tumorigenic capacity, higherproliferation in 3D cultures, lower photosensitizer accumulation andhigher cross-resistance to a chemotherapy drug with respect to parentalpopulation. The objective of this research was to identify andcompare the expression of marker proteins of CSCs in parental population,parental population after PDT (LD50) and resistant population(flow cytometry). In SCC-13, CD44+ percentage was higher inparental cells after PDT and resistant population, respect to parentalcells. In T98G was observed higher expression of CD133 markerin parental cells after PDT and in the resistant cell, comparing withparental population. Sox-2 also increased its expression in T98G(fluorescence mean 22.90 ± 3.96 U.A.) cells after PDT comparingwith parental cells (15.15± 6.43 U.A.) and SCC-13 post-PDT (335.5±160.5 U.A.) respect to parental cells (199.50 ± 65.70 U.A.). Theresults encourage us to continue the studies. We will determine thedegree of resistance of CSCs isolated with the markers CD133 andCD44. In addition, we will develop a strategy for elimination of theseCSCs resistant to PDT through a treatment with nanoparticles conjugatedto antibodies anti-CD133 and anti-CD44, in order to improvethe effectiveness of PDT.Keywords: cancer stem cells, photodynamic therapy, glioblastoma,skin cancer